35 research outputs found
Too Lucky to Be a Victim? An Exploratory Study of Online Harassment and Hate Messages Faced by Social Media Influencers
Influencers are persistently exposed through social media. Once almost unapproachable, celebrities are now open to daily interaction with the public. From comments, polls, emails, and even private messages, the public can engage with their celebrities with a mere click. While this engagement provides influencers with advantages, it also renders them particularly susceptible to online harassment and toxic critics. This paper investigates the characteristics, impact, and reactions to cyber victimisation among social media influencers. To accomplish this objective, the paper presents the findings of two studies: a self-reported online victimisation survey conducted among Spanish influencers and an online ethnography. The results indicate that over 70% of influencers have encountered some form of online harassment and toxic critics. Cyber victimisation, its effects, and reactions vary across socio-demographic characteristics and the influencers’ profiles. Furthermore, the qualitative analysis of the online ethnography reveals that harassed influencers can be classified as non-ideal victims. The implications of these findings for the literature are discussed
Externally-Controlled Systems for Immunotherapy: From Bench to Bedside
We thank GENYO Institute and LentiStem Biotech for the
support to compile of the necessary information to write this
review. We also thank Fundación Poco Frecuente (FPF) and
Asociación Española de Enfermos con Glucogenosis (AEEG) for
their kindly support.Immunotherapy is a very promising therapeutic approach against cancer that is
particularly effective when combined with gene therapy. Immuno-gene therapy
approaches have led to the approval of four advanced therapy medicinal products
(ATMPs) for the treatment of p53-deficient tumors (Gendicine and Imlygic), refractory
acute lymphoblastic leukemia (Kymriah) and large B-cell lymphomas (Yescarta). In
spite of these remarkable successes, immunotherapy is still associated with severe
side effects for CD19+ malignancies and is inefficient for solid tumors. Controlling
transgene expression through an externally administered inductor is envisioned as a
potent strategy to improve safety and efficacy of immunotherapy. The aim is to develop
smart immunogene therapy-based-ATMPs, which can be controlled by the addition
of innocuous drugs or agents, allowing the clinicians to manage the intensity and
durability of the therapy. In the present manuscript, we will review the different inducible,
versatile and externally controlled gene delivery systems that have been developed and
their applications to the field of immunotherapy. We will highlight the advantages and
disadvantages of each system and their potential applications in clinics.Spanish ISCIII Health Research FundEuropean Union (EU)
PI12/01097
PI15/02015
PI18/00337
PI18/00330CECEyUCSyF of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) for Andalusia
2016000073391-TRA
2016000073332-TRA
PI-57069
PAIDI-Bio326
PI-0014-2016Nicolas Monardes regional Ministry of Health
0006/2018Spanish Government
FPU16/05467
FPU17/02268MCI
DIN2018-01018
Genome-edited adult stem cells: Next-generation advanced therapy medicinal products
Over recent decades, gene therapy, which has enabled the treatment of several incurable
diseases, has undergone a veritable revolution. Cell therapy has also seen major advances
in the treatment of various diseases, particularly through the use of adult stem cells
(ASCs). The combination of gene and cell therapy (GCT) has opened up new opportunities to improve advanced therapy medicinal products for the treatment of several diseases. Despite the considerable potential of GCT, the use of retroviral vectors has major
limitations with regard to oncogene transactivation and the lack of physiological expression. Recently, gene therapists have focused on genome editing (GE) technologies as an
alternative strategy. In this review, we discuss the potential benefits of using GE technologies to improve GCT approaches based on ASCs. We will begin with a brief summary of
different GE platforms and techniques and will then focus on key therapeutic approaches
that have been successfully used to treat diseases in animal models. Finally, we discuss
whether ASC GE could become a real alternative to retroviral vectors in a GCT setting.European Regional Development Fund
(FEDER), Grant/Award Numbers: PI18/01610,
PI18/00330, PI18/00337, grants PI12/01097;
Spanish ISCIII Health Research Fun
Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma
Autologous T cells expressing the Chimeric Antigen Receptor (CAR) have been
approved as advanced therapy medicinal products (ATMPs) against several
hematological malignancies. However, the generation of patient-specific CART
products delays treatment and precludes standardization. Allogeneic off-theshelf
CAR-T cells are an alternative to simplify this complex and timeconsuming
process. Here we investigated safety and efficacy of knocking out
the TCR molecule in ARI-0001 CAR-T cells, a second generation aCD19 CAR
approved by the Spanish Agency of Medicines and Medical Devices (AEMPS)
under the Hospital Exemption for treatment of patients older than 25 years with
Relapsed/Refractory acute B cell lymphoblastic leukemia (B-ALL). We first
analyzed the efficacy and safety issues that arise during disruption of the TCR
gene using CRISPR/Cas9. We have shown that edition of TRAC locus in T cells
using CRISPR as ribonuleorproteins allows a highly efficient TCR disruption
(over 80%) without significant alterations on T cells phenotype and with an
increased percentage of energetic mitochondria. However, we also found that
efficient TCRKO can lead to on-target large and medium size deletions,
indicating a potential safety risk of this procedure that needs monitoring.
Importantly, TCR edition of ARI-0001 efficiently prevented allogeneic
responses and did not detectably alter their phenotype, while maintaining a
similar anti-tumor activity ex vivo and in vivo compared to unedited ARI-0001 CAR-T cells. In summary, we showed here that, although there are still some
risks of genotoxicity due to genome editing, disruption of the TCR is a feasible
strategy for the generation of functional allogeneic ARI-0001 CAR-T cells. We
propose to further validate this protocol for the treatment of patients that do
not fit the requirements for standard autologous CAR-T cells administration.Spanish ISCIII Health Research FundEuropean Commission PI15/02015
PI18/00337
PI21/00298Red TerAv RD21/ 0017/0004
PI18/ 00330
PI17/00672CECEyU and CSyF of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) for Andalusia 2016000073391-TRA
2016000073332-TRA
PI-57069
PAIDIBio326
CARTPI-0001- 201
PECART-0031-2020
PI0014-2016
PEER-0286-2019Spanish Government 00123009/SNEO-20191072
PLEC2021-008094regional Ministry of Health 0006/2018
C2-0002-2019Spanish Government FPU16/05467
FPU17/02268
FPU17/04327Junta de Andalucia PECART-00312020Consejeria de Salud y Familias PECART-0027-2020
MCI DIN2018-010180
DIN2020-01155
Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer
Several studies have suggested that single nucleotide polymorphisms (SNPs) related to
vitamin D metabolism may affect CRC carcinogenesis and survival. The aim of this study was to
evaluate the influence of 13 SNPs involved in the vitamin D metabolic pathway on CRC survival. We
conducted an observational retrospective cohort study, which included 127 Caucasian CRC patient
from the south of Spain. SNPs in VDR, CYP27B1, CYP2R1, CYP24A1, and GC genes were analyzed
by real-time polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS)
were assessed. Cox regression analysis adjusted for metastasis, age of diagnosis, stage (IIIB, IV or
IVB), ECOG score (2–4), lymph node involvement, adjuvant chemotherapy, and no family history of
CRC showed that the VDR ApaI (p = 0.036), CYP24A1 rs6068816 (p < 0.001), and GC rs7041 (p = 0.006)
were associated with OS in patients diagnosed with CRC, and CYP24A1 rs6068816 (p < 0.001) was
associated with PFS adjusted for metastasis, age of diagnosis, stage (IIIB, IV or IVB), ECOG score
(2–4), lymph node involvement, adjuvant chemotherapy, and no primary tumor resection. The rest of
the SNPs showed no association with CRC survival. Thus, the SNPs mentioned above may have a
key role as prognostic biomarkers of CRCERDF funds (EU)Instituto de Salud Carlos III (PT13/0010/0039)Biobank of the University Hospital Virgen de las Nieve
Physiological lentiviral vectors for the generation of improved CAR-T cells
Anti-CD19 chimeric antigen receptor (CAR)-T cells have
achieved impressive outcomes for the treatment of relapsed
and refractory B-lineage neoplasms.However, important limitations
still remain due to severe adverse events (i.e., cytokine
release syndrome and neuroinflammation) and relapse of
40%–50%of the treated patients.MostCAR-Tcells are generated
using retroviral vectors with strong promoters that lead to high
CAR expression levels, tonic signaling, premature exhaustion,
and overstimulation, reducing efficacy and increasing side effects.
Here, we show that lentiviral vectors (LVs) expressing the
transgene through a WAS gene promoter (AW-LVs) closely
mimic the T cell receptor (TCR)/CD3 expression kinetic upon
stimulation. These AW-LVs can generate improved CAR-T cells
as a consequence of theirmoderate andTCR-like expression profile.
Compared with CAR-T cells generated with human elongation
factor a (EF1a)-driven-LVs, AW-CAR-T cells exhibited
lower tonic signaling, higher proportion of naive and stem cell
memory T cells, less exhausted phenotype, and milder secretion
of tumor necrosis factor alpha (TNF-a) and interferon (IFN)-ɣ
after efficient destruction of CD19+ lymphoma cells, both
in vitro and in vivo.Moreover, we also showed their improved efficiency
using an in vitro CD19+ pancreatic tumor model. We
finally demonstrated the feasibility of large-scale manufacturing
ofAW-CAR-T cells in good manufacturing practice (GMP)-like
conditions. Based on these data, we propose the use of AW-LVs
for the generation of improved CAR-T products.Spanish ISCIII Health Research FundEuropean Commission PI15/02015
PI18/00337
PI21/00298
RD21/0017/0004
PI18/00330
PI17/00672CSyF of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) for Andalusia 2016000073391-TRA
2016000073332-TRA
PI-57069
PA IDI-Bio326
CARTPI-0001-201
PECART-0031-2020
Red RANTECAR CAR-T 2019 00400200101918
PLEC2021-008094
PI-0014-2016
PEER-0286-2019Spanish Government PLEC2021-008094
00123009/SNEO-20191072Nicolas Monardes contracts from regional Ministry of Health 0006/2018
C2-0002-2019German Research Foundation (DFG) FPU16/05467
FPU17/02268
FPU17/04327
MCI DIN2018-010180Fundacion Andaluza Progreso y SaludGerman Research Foundation (DFG) PEJ-2018-001760-AJunta de Andalucia PE-0223-2018Biomedicine Programme of the University of Granada (Spain
Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells
Controlling transgene expression through an externally
administered inductor is envisioned as a potent strategy
to improve safety and efficacy of gene therapy approaches.
Generally, inducible ON systems require a chimeric transcription
factor (transactivator) that becomes activated by
an inductor, which is not optimal for clinical translation
due to their toxicity. We generated previously the first
all-in-one, transactivator-free, doxycycline (Dox)-responsive
(Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control
transgene expression in human stem cells. Here, we
have generated new versions of the LOP LVs and have
analyzed their applicability for the generation of inducible
advanced therapy medicinal products (ATMPs) with special
focus on primary human T cells. We have shown that, contrary
to all other cell types analyzed, an Is2 insulator must
be inserted into the 30 long terminal repeat of the LOP
LVs in order to control transgene expression in human
primary T cells. Importantly, inducible primary T cells
generated by the LOPIs2 LVs are responsive to ultralow
doses of Dox and have no changes in phenotype or function
compared with untransduced T cells. We validated
the LOPIs2 system by generating inducible CAR-T cells
that selectively kill CD19+ cells in the presence of Dox.
In summary, we describe here the first transactivatorfree,
all-one-one system capable of generating Dox-inducible
ATMPs.Spanish ISCIII Health Research FundEuropean Union (EU) PI18/00337
PI21/00298
RD21/0017/0004
PI18/00330
PI17/00672Red TerAvJunta de Andalucia FEDER/European Cohesion Fund (FSE) for AndalusiaSpanish Government PI18/00337
PI21/00298European Union-NextGenerationEU - Maria Zambrano Senior Program RD21/0017/0004
PI18/00330
PI17/00672Ministry of Health 2016000073332-TRA
PI-57069
CARTPI-0001-201
PE-CART-0031-2020
PI-0014-2016
PECART-0027-2020
ProyExcel_00875
PEER-0286-2019European Cooperation in Science and Technology (COST) 00123009/SNEO-20191072MINECO - European Regional Development Fund PLEC2021-008094Spanish Government 0006/2018FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades CA21113Spanish Government SAF2015-71589-PMCI RYC-2016-21395German Research Foundation (DFG) PY20_00619 y A-CTS-28_UGR20Biomedicine Program of the University of Granada (Spain) FPU16/05467
FPU17/02268
FPU17/04327
DIN2018-010180
DIN2020-011550
PEJ-2018-001760-
Agenda de investigación: Smart cities y seguridad en Andalucía
Este documento forma parte del proyecto de investigación "Tecnología y control social: Fundamentos de la gobernanza democrática de la seguridad en Andalucía" PAIDI 2020-PI00941La gobernanza de la seguridad en las Smart cities supone un gran reto a nivel de diseño, planificación y gestión. El número de investigadores y grupos de investigación andaluces en esta temática es aún escaso, lo que puede dificultar avanzar de manera significativa y lograr un impacto científico y una competitividad y transferencia internacional de conocimiento. Por eso uno de los objetivos de este proyecto era establecer una agenda de investigación que permitiera identificar hacia la comunidad de investigadores aquellos temas de mayor relevancia con vistas a focalizar los recursos y generar sinergias entre ellos. Además, el futuro próximo de la gestión de la seguridad en las Smart cities requerirá, sin lugar a dudas, un trabajo multidisciplinar que aglutine a investigadores de diferentes campos, así como a la industria y al sector público, lo que debería favorecer que se lancen iniciativas coherentes y se establezcan líneas de investigación sólidas.Proyecto cofinanciado en un 80% por la Unión Europea, en el marco del Programa Operativo FEDER Andalucía 2014-2020 «Crecimiento inteligente: una economía basada en el conocimiento y la innovación».
Proyecto financiado por la Consejería de Transformación Económica, Industria, Conocimiento y Universidades. Código P20-00941Informe de 8 páginas fruto de un taller realizado el 6 de marzo de 202
Geodivulgar: Geología y Sociedad
Con el lema “Geología para todos” el proyecto Geodivulgar: Geología y Sociedad apuesta por la divulgación de la Geología a todo tipo de público, incidiendo en la importancia de realizar simultáneamente una acción de integración social entre estudiantes y profesores de centros universitarios, de enseñanza infantil, primaria, de educación especial y un acercamiento con público con diversidad funcional